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    ClodronateLiposomes英文版產品原理介紹

    更新時間:2022-12-18   點擊次數:1421次

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    Introduction

    The chemical depletion of macrophages is a powerful research method for a comprehensive understanding of macrophage function under pathological conditions. Clodronate Liposomes is a mature, convenient and economical macrophage removal tool, which can effectively remove macrophages in different tissues and blood in animals. Clodronate liposomes was developed by Professor Nico van rooijen of Vrije University in Amsterdam, the Netherlands.

    Composition and Mechanism

    Clodronate disodium (Clodronate) is a bisphosphonate drug, which is mainly used clinically for osteolytic bone metastases, osteoporosis and hypercalcemia caused by cancer. It is metabolized into non-hydrolyzable ATP analogs in cells, inhibiting the ADP/ATP transport mechanism in mitochondria, thereby blocking the mitochondrial respiratory chain and inducing apoptosis. However, the drug has low lipophilicity and cannot be transported across cells. After oral or intravenous administration of free drug, the half-life can be reached after 2 hours, and 80% of the drug is excreted in urine within 48 hours. Therefore, it is difficult to directly reach a sufficient concentration in vivo. However, once encapsulated in liposomes, clodronate can allow a specific targeting of the phagocytic cells. Liposomes are rapidly recognized and phagocytosed by macrophages, permitting a threshold of effective clodronate concentration to trigger apoptosis in target cells.

    Fig. 1 Clodronate liposomes complex

    After injection into the organism, the clodronate liposome will be phagocytosed by macrophages, and under the action of lysosomal phosphatase in the macrophage, the clodronate dissolved in the liposome will be gradually released and released. It accumulates in cells, and when it reaches a certain concentration, macrophages will be irreversibly damaged and apoptosis will be induced. Clodronate in dead cells is released extracellularly and excreted in the urine.

    Advantages of Standard-Clodronate-Liposomes

    The standard clodronate liposomes has many superior properties such as high activity, long validity, ease of use, sterility and non-toxicity. Advantages of this dosage form include high concentration, high encapsulation rate, non-sticky, non-sedimentation, ease of injection, etc. and high activity and uniformity without sedimentation even after months of storage in the refrigerator. And it is suitable for a variety of routes of administration, including intravenous, intraperitoneal, subcutaneous, tracheal and direct injection.

    Recommendations

    - The product must be removed from the vial using sterile technique. Do not use if sterility is compromised.

    - Liposomes may settle when left undisturbed for more than a few hours. Immediately prior to use, in order to ensure a homogeneous liposome suspension, slowly invert the vial several times until the suspension appears homogeneous by visual inspection.

    - Liposomes should be kept at 4°C and never be frozen.

    - Dilution is not recommended, unless required for special experiments.

    - The reagents must not come into contact with organic reagents such as chloroform, methanol, ethanol, etc., otherwise the liposome structure will be destroyed.

    - The reagent must not come into contact with surface detergents or surfactants, otherwise the liposome structure will be destroyed.

    - Do not heat, near or above the main phase transition temperature of the lipid, except for drug loading, which requires incubation above the phase transition temperature.

    Reference

    1. Van Rooijen N; et al. Liposomes for specific depletion of macrophages from organs and tissues. Methods Mol Biol. 2010; 605: 189–203.


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